Blood brain barrier

The blood-brain barrier (BBB) is of pivotal importance in maintaining homeostasis of the central nervous system (CNS), as it closely regu- lates the composition of the interstitial fluid in the brain (Nienke et al., 2006). The BBB at the level of brain microvessels creates the largest surface area known as the ‘barrier interface’ (12-20 m2/1.3 kg of brain) and has the greatest influence on drug delivery to the brain. It is the most important site for regulating drug access to the brain, given its large surface area and the short diffusion distances from capillaries to neurons (10-15 µm) (Nienke et al., 2006).

The experimental determination of logBB (blood-brain barrier) is a time-consuming, expensive and dif- ficult technique, requiring animal experiments and the synthesis of the test compounds, usually in radiola- beled form (Schlageter et al., 1999; Chikhale et al.,1994). It is of considerable value to predict logBB val- ues of compounds from their physicochemical param- eters or, ideally, from their molecular structures.

So, the value ascribed to this ability is calculated as demonstrated by Clark (Clark and Patrick, 2000).

LogBB = -0.0148 (PSA, Polar Surface Area) + 0.152 log P + 0.139

References:

1. Nienke de VA, Beijnen JH, Boogerd W, Tellingen OV (2006). Blood- brain barrier and chemotherapeutic treatment of brain tumors. Exp Rev. 6: 1199-1209.

2. Clark DE, Pickett SD (2000). Computational Prediction for the prediction of ‘drug likeness’. Drug Discov Today. 5: 49-58.